Coexistence of EphB1 and EphrinB2 in Port Wine Stain Endothelial Progenitor Cells Contributes to Clinicopathological Vasculature Dilatation

Abstract

Port wine stain (PWS) is a vascular malformation characterized by a progressive dilatation of post-capillary venules, but the molecular pathogenesis remains obscure. We hypothesized that PWS endothelial cells (ECs) present a unique molecular phenotype that lead to pathoanatomic PWS vasculatures. We herein show multiple clinicopathologic features of PWS blood vessels during the development and progression of the disease. 1) There were no normal arterioles and venules phenotypically and morphologically observed in PWS skin; both arterioles and venules showed differentiation impairments, resulting in a reduction of arteriole-like vasculatures and defects in capillary loop formation in PWS lesions. 2) PWS ECs showed stemness properties with expression of endothelial progenitor cell markers CD133 and CD166. They also expressed dual venous/arterial identities, EphB1 and ephrinB2. 3) Co-expression of EphB1 and ephrinB2 in normal human dermal microvascular ECs led to formation of PWS-like vasculatures in vitro, e.g. larger diameter and thick-wall capillaries. We concluded that PWS ECs are differentiation-impaired late stage endothelial progenitor cells with a specific phenotype of CD133⁺/CD166⁺/ EphB1⁺/ephrinB2⁺ which form immature venule-like pathoanatomic vasculatures. The disruption of normal EC-EC interactions by co-existence of EphB1 and ephrinB2 contributes to progressive dilatation of PWS vasculatures.

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